Hardin J A, Gibson M, Grant E, Sherr D H
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Proc Soc Exp Biol Med. 1992 Jul;200(3):383-93. doi: 10.3181/00379727-200-43446.
CD5+ B cells have been shown to be disproportionately associated with autoimmune diseases and transformation. In many cases, their apparent ability to bypass self-tolerance is manifested by the production of autoantibodies. These observations, plus the hypothesis that CD5+ B cells represent a distinct B cell lineage, encourage studies into the conditions and factors that influence their development. In the present study, we employed a well-established assay for murine CD5+ B cell function, i.e., their ability to augment the responses of IgHb-linked idiotypic determinants on anti-(4-hydroxy-3-nitrophenyl) acetyl (NP) antibody (Nbb) idiotype-bearing CD5- B cells to a T-independent antigen, together with multiple methods of cell surface phenotyping, to evaluate the potential for interleukin (IL) 4 to effect maturation of CD5+ B cells, CD5+, IgM+, Thy-1-, and NPb idiotype-specific cells panned on antibody-coated petri dishes or sorted by flow cytometry from spleen were capable of augmenting NPb idiotypic responses of NP-KLH-primed responder cells to NP-Ficoll. Splenic B cell populations depleted of CD5+ B cells failed to affect idiotype expression even after 2 days in culture, a time when a small percentage of CD5+ B cells appeared to be regenerated. However, idiotype-specific regulatory activity could be restored in CD5- splenic B cell populations by culture for 2 days with recombinant IL-4. Cells responsible for idiotype-specific regulatory activity after culture with IL-4 were in fact CD5+, IgM+, and Thy-1.2- B cells, demonstrating that IL-4 can drive the functional, if not the phenotypic, maturation of splenic B cells associated with the CD5+ B cell lineage. The results illustrate one possible mechanism by which T cells could control the maturation of cells belonging to the CD5+ B cell lineage.
已表明CD5⁺ B细胞与自身免疫性疾病和细胞转化存在不成比例的关联。在许多情况下，它们绕过自身耐受的明显能力表现为自身抗体的产生。这些观察结果，再加上CD5⁺ B细胞代表一种独特的B细胞谱系这一假设，促使人们对影响其发育的条件和因素进行研究。在本研究中，我们采用了一种成熟的小鼠CD5⁺ B细胞功能检测方法，即它们增强抗（4 - 羟基 - 3 - 硝基苯基）乙酰（NP）抗体（Nbb）独特型携带的CD5⁻ B细胞上与IgHb相关的独特型决定簇对T细胞非依赖性抗原反应的能力，同时结合多种细胞表面表型分析方法，来评估白细胞介素（IL）4影响CD5⁺ B细胞成熟的潜力。在抗体包被的培养皿上淘选或通过流式细胞术从脾脏中分选出来的CD5⁺、IgM⁺、Thy - 1⁻和NPb独特型特异性细胞能够增强NP - KLH免疫的应答细胞对NP - 菲可的NPb独特型反应。即使在培养2天后，耗尽CD5⁺ B细胞的脾B细胞群体也未能影响独特型表达，此时有一小部分CD5⁺ B细胞似乎再生了。然而，通过用重组IL - 4培养2天，CD5⁻脾B细胞群体中的独特型特异性调节活性可以恢复。用IL - 4培养后负责独特型特异性调节活性的细胞实际上是CD5⁺、IgM⁺和Thy - 1.2⁻ B细胞，这表明IL - 4可以驱动与CD5⁺ B细胞谱系相关的脾B细胞的功能成熟（即使不是表型成熟）。这些结果说明了T细胞控制属于CD5⁺ B细胞谱系的细胞成熟的一种可能机制。
